Juncus roemerianus hemostatic gauze and preparation method thereof

Abstract

The invention provides juncus roemerianus hemostatic gauze and a preparation method thereof, and belongs to the field of medical dressing preparation.The preparation method comprises the steps that PVA is dissolved in water, and a polyvinyl alcohol solution with the concentration being 5-15% wt is prepared; grinding the juncus roemerianus subjected to alkali treatment into powder, adding the powder into a polyvinyl alcohol solution, then adding a cross-linking agent solution, and uniformly stirring to obtain a mixed solution; uniformly coating gauze with the mixed solution, and then performing freeze thawing treatment for 2-4 times to obtain the juncus roemerianus hemostatic gauze. According to the method, the haemostatic gauze is directly prepared from the juncus roemerianus powder, the process is simple, the cost is low, and the haemostatic effect is good. The Juncus roemerianus with the three-dimensional net-shaped porous structure and PVA jointly form a gel skeleton, and the fiber grid structure of the medical gauze is wrapped in the skeleton, so that the hemostatic material can be prevented from falling off in the use process, and meanwhile, the adhesion of the gauze to a wound surface is moderately improved.

Description

Technical Field

[0001] The invention relates to the technical field of medical dressing preparation, in particular to rush hemostatic gauze and a preparation method thereof. Background Art

[0002] The hemostatic mechanism of gauze is mainly achieved through the dual effects of physical compression and biological activity activation. Among them, the woven structure of the gauze can slow down blood flow by directly compressing the broken ends of blood vessels in the wound. The hydrophilicity of the gauze can enable it to quickly absorb water from the blood, concentrate platelets and coagulation factors, and promote local thrombosis. The rough fiber surface damages platelets, exposes their phospholipid membranes, triggers the coagulation cascade reaction, and accelerates platelet aggregation and the construction of a fibrin cross-linking network. In addition, the fiber grid structure of the gauze can also provide an attachment skeleton for blood cells and fibrin to form a blood clot barrier that mechanically closes the wound.

[0003] There are many types of hemostatic gauze in the prior art, such as chitosan hemostatic gauze, calcium alginate hemostatic gauze, thrombin-containing hemostatic gauze, etc. However, some hemostatic products may cause allergic reactions or have adverse effects on wound healing. For example, calcium alginate hemostatic gauze may cause foreign body reactions, and alginate fibers remaining in the wound may cause chronic symptomatic foreign body giant cell reactions. In addition, some hemostatic products also have problems such as insufficient hemostatic performance, easy adhesion to the wound causing secondary damage, or poor adhesion and inability to fit tightly to the wound. Chinese patent publication number CN102120043B proposes a degreased cotton gauze containing nanosilver and chitosan and its preparation device and method. The degreased cotton gauze contains cationic polysaccharides with good antibacterial properties and nanosilver. Chitosan is combined with medical degreased cotton gauze by soaking and freeze-drying. Nanosilver is adsorbed on the gauze through the interaction between nanosilver particles and chitosan amino groups. The chitosan and nanosilver components achieve long-lasting and efficient bactericidal performance. However, the preparation cost of this absorbent cotton gauze is high.

[0004] In view of this, it is necessary to design a rush hemostatic gauze and a preparation method thereof to solve the above technical problems. Summary of the Invention

[0005] In view of the technical problems existing in the background technology, the present application provides a rush hemostatic gauze and a preparation method thereof, aiming to solve the technical problems of insufficient hemostatic performance, poor compatibility, and high cost of some hemostatic gauzes.

[0006] In a first aspect, the present invention provides a method for preparing a rush hemostatic gauze, comprising the following steps: S1, mixing polyvinyl alcohol (PVA) and water under stirring conditions, standing at room temperature for a period of time, heating in a water bath and stirring to fully dissolve the polyvinyl alcohol to obtain a polyvinyl alcohol solution with a concentration of 5-15%wt; S2, grinding the alkali-treated rush into powder, mixing it with the polyvinyl alcohol solution obtained in step S1 and stirring it evenly, then adding the crosslinking agent solution, and continuing to stir evenly to obtain a mixed solution; S3, evenly coating the mixed solution obtained in step S2 on gauze, and then performing freeze-thaw treatment 2-4 times to obtain rush hemostatic gauze.

[0007] In the technical scheme of the present application embodiment, with PVA as matrix, after powdered rush is mixed with PVA solution, it is evenly coated on medical gauze, prepares rush hemostatic gauze through circulation freeze-thaw process.Wherein, PVA solution concentration is too low (such as being less than 5%wt) or too high (such as being greater than 15%wt) and all can cause the adhesive force of gauze to decline, and the porosity of the gel layer that the too high concentration can cause gauze fiber surface to wrap is reduced, and the air permeability variation of gauze, and feel is hard.In addition, when PVA concentration is 10%, the hemostatic effect of gauze is best, on the one hand, when PVA concentration is 10%, the adhesiveness of gauze is best, can be closely fitted with wound surface, avoid the gap oozing blood caused by deformation in use, can better adsorb blood simultaneously, promote coagulation factor to gather.On the other hand, when PVA concentration is 10%, the porosity of the gel layer that gauze surface wraps is high, and pore connectivity is better, can rapidly adsorb blood, improve hemostasis efficiency.

[0008] In some embodiments, the mass ratio of rush to polyvinyl alcohol is 1:(0.67-1.5).

[0009] In this embodiment, if the proportion of rush is too low, it will affect the antibacterial and hemostatic properties of the gauze. If the proportion is too high, it will easily precipitate in the mixed solution and on the gauze, affecting the uniformity of the powder distribution in the gauze, and further affecting the air permeability and feel of the gauze. The gauze with precipitation will feel hard.

[0010] In some embodiments, in step S3, the freeze-thaw treatment step includes freezing at -(15-25)°C for 12-16 hours, and then taking it out and thawing it at room temperature for 2-4 hours.

[0011] In this embodiment, the freeze-thaw treatment facilitates the formation of a porous physical structure through the nucleation, growth, and melting of ice crystals, significantly improving the mechanical strength, porosity, and stability of the gel, making it more suitable for hemostasis. Cyclic freeze-thaw treatment gradually optimizes the microstructure and macroscopic properties of the gel structure through multiple physical actions. Large ice crystals are fragmented through repeated crystallization-thawing processes, i.e., the size of the ice crystals is gradually reduced. During the melting process, the ice crystals melt and release some stress, and the polymer chains partially rebound and reorganize, forcing the molecular chains to rearrange to form a more uniform nanofiber network. This also promotes an increase in the density of cross-linking points, ultimately resulting in a gel with higher mechanical strength, more uniform structure, and more stable function.

[0012] In some embodiments, in step S1, the temperature of the water bath heating and stirring is 80-90°C, and the time is greater than or equal to 30 minutes; in step S1, standing at room temperature for a period of time specifically refers to standing at room temperature for 20-60 minutes.

[0013] In this embodiment, heating the mixture in a water bath to 80-90°C with stirring and maintaining the temperature for 30 minutes or longer is primarily intended to disrupt the crystalline regions of the PVA and overcome intermolecular hydrogen bonds to fully dissolve the PVA. The purpose of allowing the mixture to stand at room temperature is to pre-swell the PVA, thereby shortening the subsequent water bath heating time.

[0014] In some embodiments, in step S2, the rush is polished and then sieved using a 300-700 mesh sieve.

[0015] In this embodiment, if the rush powder particle size is too coarse, the powder will settle in the mixed solution, affecting the uniformity of the powder distribution in the gauze. At the same time, if the rush powder is too coarse, the three-dimensional skeleton structure formed with PVA will be unstable, that is, the gel layer wrapped on the gauze will easily fall off. If the rush powder particle size is too fine, it will easily agglomerate, which will also affect the uniformity of the powder distribution in the gauze and cause clogging of the pores, affecting the air permeability of the gauze.

[0016] In some embodiments, in step S2, the cross-linking agent is a mixture of citric acid and sodium hypophosphite.

[0017] In some embodiments, the mass ratio of the citric acid to the sodium hypophosphite is (3-1):1.

[0018] In this embodiment, the mixture of citric acid and sodium hypophosphite plays a major role in synergistic crosslinking and catalytic esterification in the preparation of rush hemostatic gauze. The carboxyl groups (-COOH) on the citric acid can form a covalent crosslinked network with the hydroxyl groups (-OH) on PVA or rush through a high-temperature esterification reaction, enhancing the skeleton strength of the gel wrapped on the gauze surface. The sodium hypophosphite acts as a reducing agent and esterification catalyst, on the one hand inhibiting the oxidative degradation of citric acid at high temperatures, and on the other hand accelerating the formation of ester bonds (-COOR) by reducing the activation energy of the esterification reaction, thereby improving crosslinking efficiency.

[0019] In some embodiments, in step S2, the specific steps of alkali treatment include placing the rush in an alkaline solution and heating it for 15-25 minutes, taking it out and washing it with water, then placing it in the alkaline solution again and heating it for 15-25 minutes, taking it out and washing it with water until no alkaline solution remains, then placing it in water and heating it for 10-25 minutes, and drying it.

[0020] In this embodiment, alkali treatment can destroy the hydrophobic lignin and hemicellulose on the surface of rush, and at the same time cause the cellulose chains to swell to expose more polar hydroxyl groups (-OH), thereby increasing the hydrophilicity of rush, promoting the uniform dispersion of rush in PVA solution, and the subsequent cross-linking reaction.

[0021] In a second aspect, an embodiment of the present application provides a rush hemostatic gauze, which is prepared according to the method for preparing rush hemostatic gauze described in any one of the aforementioned technical solutions. A gel skeleton formed by cross-linking rush and PVA wraps the gauze fibers inside.

[0022] The beneficial effects of this application are as follows: The present application provides a rush hemostatic gauze and a preparation method thereof, wherein PVA is used as a matrix, powdered rush is mixed with a PVA solution and then evenly coated on medical gauze, and the rush hemostatic gauze is prepared through a cyclic freeze-thaw treatment. The present application adopts a method of first coating a mixed solution and then performing a cyclic freeze-thaw treatment, successfully attaching rush to the gauze in powder form evenly and firmly. In the rush hemostatic gauze, the rush and PVA with a three-dimensional mesh porous structure together form a stable gel three-dimensional skeleton, and the fiber grid structure of the medical gauze is wrapped inside the skeleton, which can avoid the shedding of the gel hemostatic material during use, and at the same time moderately increase the adhesion of the gauze, ensuring that the gauze fits tightly to the wound surface to fully exert the hemostatic effect, and avoids secondary damage due to excessive adhesion.

[0023] The preparation method provided in this application directly uses rush powder to prepare hemostatic gauze without the need for extraction or synthesis. The process is simple and the cost is low. It also achieves a good hemostatic effect and has broad application prospects. During the preparation process, this application also regulates the preparation conditions such as PVA concentration, the mass ratio of rush to PVA, and the particle size of rush powder to adjust the prepared gel structure to balance the antibacterial hemostatic performance and feel of the hemostatic gauze. When the PVA concentration is 10%, the mass ratio of rush to PVA is 1:1, and the rush particle size is ≤30.8μm (using a 500 mesh sieve), the rush hemostatic gauze has the best hemostatic effect and structural stability, and the adsorption force is moderate. In actual applications, the encapsulated gel structure formed on the gauze surface when the PVA concentration is 10% has both density and flexibility, which can support the uniform distribution of rush powder and seal the wound through moderate swelling. The adhesion is 0.3N / cm higher than that of ordinary gauze. 3 The hemostatic time and bleeding volume are only half of those of ordinary gauze. The hemostatic time is 58s shorter than that of chitosan hemostatic gauze, and the bleeding volume is 0.36g less.

[0024] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application, it can be implemented in accordance with the contents of the specification. In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] To more clearly illustrate the technical solution of this application, the following is a brief introduction to the drawings used in this application. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be derived from these drawings without inventive effort.

[0026] Figure 1 A physical picture of the rush hemostatic gauze prepared in Examples 1-3 of the present application; Figure 2 This is a scanning electron microscope (SEM) image of the rush hemostatic gauze prepared in Example 1 and Example 4 of the present application; Figure 3 This is a physical picture of the rush hemostatic gauze prepared in Example 7 of the present application. DETAILED DESCRIPTION

[0027] The following embodiments of the technical solution of the present application will be described in detail with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present application and are therefore only examples and are not intended to limit the scope of protection of the present application.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application belongs; the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit this application; the terms "including" and "having" and any variations thereof in the specification and claims of this application and the above-mentioned figure descriptions are intended to cover non-exclusive inclusions.

[0029] In the description of the embodiments of this application, the technical terms "first" and "second" are used only to distinguish different objects and should not be understood to indicate or imply relative importance or implicitly specify the quantity, specific order, or primary and secondary relationship of the indicated technical features. In the description of the embodiments of this application, the meaning of "plurality" is more than two, unless otherwise clearly and specifically defined.

[0030] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0031] In the description of the embodiments of this application, the term "and / or" is merely a description of the association relationship between associated objects, indicating that three relationships can exist. For example, A and / or B can represent three situations: A exists alone, A and B exist at the same time, and B exists alone. In addition, the character " / " in this document generally indicates that the associated objects are in an "or" relationship. For those of ordinary skill in the art, the specific meanings of the above terms in the embodiments of this application can be understood according to specific circumstances.

[0032] There are many types of hemostatic gauze available in the art, such as chitosan gauze, calcium alginate gauze, and thrombin-containing gauze. However, some hemostatic gauze products may cause allergic reactions or adversely affect wound healing. For example, calcium alginate gauze may cause a foreign body reaction, and residual alginate fibers in the wound may cause a chronic, symptomatic foreign body giant cell reaction. Furthermore, some hemostatic products suffer from insufficient hemostatic properties, are prone to adhesion to the wound, causing secondary damage, and have high production costs.

[0033] In order to solve the technical problems of insufficient hemostatic performance, poor compatibility, and high cost of some hemostatic gauze, the present application provides a rush hemostatic gauze and a preparation method thereof, using PVA as a matrix, mixing powdered rush with a PVA solution and evenly coating it on medical gauze, and preparing the rush hemostatic gauze through a cyclic freeze-thaw process. The present application adopts a method of first coating a mixed solution and then performing a cyclic freeze-thaw process, successfully attaching rush to the gauze in the form of powder evenly and firmly. In the rush hemostatic gauze, the rush and PVA with a three-dimensional mesh porous structure together form a stable gel three-dimensional skeleton, and the fiber grid structure of the medical gauze is wrapped inside the skeleton, which can avoid the shedding of the gel hemostatic material during use, and at the same time moderately increase the adhesion of the gauze, ensuring that the gauze is closely fitted to the wound surface to give full play to the hemostatic effect, and avoid secondary damage due to excessive adhesion.

[0034] In a first aspect, the present invention provides a method for preparing a rush hemostatic gauze, comprising the following steps: S1, polyvinyl alcohol (PVA) and water are mixed under stirring conditions, allowed to stand at room temperature for a period of time, and then heated in a water bath with stirring to fully dissolve the polyvinyl alcohol to obtain a PVA solution with a concentration of 5-15%wt.

[0035] S2, grinding the alkali-treated rush into powder, mixing it with the PVA solution obtained in step S1 and stirring it evenly, then adding the crosslinker solution, and continuing to stir evenly to obtain a mixed solution.

[0036] S3, evenly coating the mixed solution obtained in step S2 on gauze, and then performing freeze-thaw treatment 2-4 times to obtain rush hemostatic gauze.

[0037] The preparation method provided by the application is with PVA as matrix, and powdered rush is evenly coated on medical gauze after being mixed with PVA solution, and rush hemostatic gauze is prepared through cyclic freeze-thaw process.The most suitable concentration range of PVA solution is 5-15%wt, preferably 10%wt.When PVA concentration is too low (such as being less than 5%wt), the gel skeleton structure wrapped in gauze fiber surface is loose and mechanical strength is insufficient, and after swelling, easily causes contact area to be reduced due to self deformation, and interfacial force weakens, and then causes adhesion to decline; When PVA concentration is too high (such as being greater than 15%wt), molecular chain excessively gathers and forms the dense layer with stronger rigidity, causes the gel layer flexibility wrapped in gauze fiber surface to decline, and the degree of conformity with wound surface is reduced (adhesion is reduced), and simultaneously, due to porosity reduction, the air permeability variation of gauze, and feel is harder. The gauze's hemostatic effect was optimal at a PVA concentration of 10%. On the one hand, when the PVA concentration was 10%, the gauze had optimal adhesion, allowing it to adhere closely to the wound surface, avoiding interstitial bleeding caused by deformation during use. It also better absorbed blood and promoted the aggregation of coagulation factors. On the other hand, when the PVA concentration was 10%, the gel layer wrapped around the gauze surface had a high porosity and good pore connectivity, allowing it to quickly absorb blood and improve hemostasis efficiency.

[0038] In some embodiments, in step S1, standing at room temperature for a period of time specifically refers to standing at room temperature for 20-60 minutes, and heating in a water bath with stirring at a temperature of 80-90° C. for a time greater than or equal to 30 minutes.

[0039] In the technical solution of the embodiment of the present application, the purpose of standing at room temperature is to pre-swell the PVA, which is conducive to shortening the time of subsequent water bath heating. The water bath is heated to 80-90°C and stirred, and the temperature is maintained for greater than or equal to 30 minutes mainly to destroy the crystalline region of PVA and overcome the intermolecular hydrogen bonding to fully dissolve the PVA. There are strong hydrogen bonds and partial crystalline structures between the PVA molecular chains, which are difficult to be fully penetrated and swelled by water molecules at room temperature. At a temperature of 80-90°C (close to the melting point of PVA), thermal energy can soften the crystalline region, weaken the hydrogen bonds, and allow water molecules to penetrate deep into the polymer chains to achieve swelling. The treatment time of water bath heating and stirring for ≥30 minutes can ensure that the crystalline region of PVA is fully melted to form a uniform, transparent, viscous solution. Too low a treatment temperature or insufficient treatment time will result in incomplete dissolution of PVA, resulting in the final PVA solution containing undissolved particles or gel clumps.

[0040] In some embodiments, in step S2, the alkali treatment comprises placing the rush in an alkaline solution and heating it for 15-25 minutes, removing it and rinsing it with water, then placing it in the alkaline solution again and heating it for 15-25 minutes, removing it and rinsing it with water until no alkaline solution remains, then placing it in water and heating it for 10-25 minutes, and drying it. The alkaline solution can be a sodium hydroxide solution or a potassium hydroxide solution, and the concentration of the alkaline solution is 0.5-2 mol / L. The drying temperature is less than or equal to 65°C.

[0041] In the technical solution of the embodiment of the present application, the hydrophobic lignin and hemicellulose on the surface of rush can be destroyed by alkali treatment, while the cellulose chains are swollen to expose more polar hydroxyl groups (-OH), thereby increasing the hydrophilicity of rush, promoting the uniform dispersion of rush in PVA solution, and the subsequent cross-linking reaction.

[0042] In some embodiments, in step S2, after being polished, the rush is sieved through a 300-700 mesh sieve (powder particle size ≤ 51.3 μm), preferably a 400-600 mesh sieve (powder particle size ≤ 38.5 μm), and further preferably a 500 mesh sieve (powder particle size ≤ 30.8 μm).

[0043] In the technical solution of the embodiment of the present application, if the powder particle size of rush is too coarse, the powder will settle in the mixed solution, affecting the uniformity of the powder distribution in the gauze. At the same time, if the rush powder is too coarse, the three-dimensional skeleton structure formed with PVA will be unstable, that is, the gel layer wrapped on the gauze will easily fall off. If the powder particle size of rush is too fine, it will easily agglomerate, which will also affect the uniformity of the powder distribution in the gauze and cause clogging of the pores, affecting the air permeability of the gauze.

[0044] In some embodiments, in step S2, the crosslinking agent is a mixture of citric acid and sodium hypophosphite. Furthermore, the mass ratio of citric acid to sodium hypophosphite is (3-1):1, preferably 2:1.

[0045] In some embodiments, in step S2, the amount of the cross-linking agent used is 0.5-0.1% of the total mass of PVA and rush.

[0046] In the technical solution of the embodiment of the present application, the mixture of citric acid and sodium hypophosphite plays a major role in synergistic crosslinking and catalytic esterification in the preparation of rush hemostatic gauze. The carboxyl groups (-COOH) on the citric acid can form a covalent crosslinked network with the hydroxyl groups (-OH) on PVA or rush through a high-temperature esterification reaction, thereby enhancing the skeleton strength of the gel wrapped on the gauze surface; the sodium hypophosphite acts as a reducing agent and esterification catalyst, on the one hand inhibiting the oxidative degradation of citric acid at high temperatures, and on the other hand accelerating the formation of ester bonds (-COOR) by reducing the activation energy of the esterification reaction, thereby improving the crosslinking efficiency.

[0047] In some embodiments, the mass ratio of rush to PVA is 1:(0.67-1.5), preferably 1:(0.8-1.2), and further preferably 1:1.

[0048] In the technical solution of the embodiment of the present application, if the proportion of rush is too low, it will affect the antibacterial and hemostatic properties of the gauze. If the proportion is too high, it will easily precipitate in the mixed solution and on the gauze, affecting the uniformity of the powder distribution in the gauze, and then affecting the air permeability and feel of the gauze. The gauze with precipitation feels hard.

[0049] In some embodiments, in step S3, the freeze-thaw treatment step includes freezing at -(15-25)°C for 12-16 hours, and then taking it out and thawing it at room temperature for 2-4 hours.

[0050] In the technical solution of the embodiment of the present application, the freeze-thaw treatment is conducive to the formation of a porous physical structure through the nucleation, growth, and melting of ice crystals, significantly improving the mechanical strength, porosity, and stability of the gel, making it more in line with the needs of hemostasis. The cyclic freeze-thaw treatment is to gradually optimize the microstructure and macroscopic properties of the gel structure through multiple physical actions, and to fragment the large ice crystals through repeated crystallization-thawing processes, that is, the size of the ice crystals is gradually reduced. During the melting process, the ice crystals melt and release some stress, and the polymer chains partially rebound and reorganize, forcing the molecular chains to rearrange to form a more uniform nanofiber network, while promoting the increase in the density of cross-linking points, and ultimately obtaining a gel with higher mechanical strength, more uniform structure, and more stable function.

[0051] In a second aspect, an embodiment of the present application provides a rush hemostatic gauze, which is prepared by any of the preparation methods described in the aforementioned schemes. The rush and PVA are cross-linked to form a gel skeleton that wraps the gauze fibers inside.

[0052] Some specific examples are listed below. It should be noted that the examples described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. Where specific techniques or conditions are not specified in the examples, the techniques or conditions described in the literature in this area or the product specifications are used. Reagents or instruments used without manufacturer's indication are all commercially available conventional products.

[0053] Example 1 Example 1 provides a method for preparing rush hemostatic gauze, comprising the following steps: S1. Weigh 22.22 g of 1799 polyvinyl alcohol (PVA) particles into a beaker. Slowly add 200 ml of pure water while stirring. After standing at room temperature for 30 min, place the beaker in a water bath at 80-90°C and slowly stir for 30 min to fully dissolve the polyvinyl alcohol to obtain a PVA solution with a concentration of 15% wt.

[0054] S2, put an appropriate amount of rush into an alkaline solution and heat it for about 20 minutes, then take it out and wash it with water, then put it into the alkaline solution again and heat it for 20 minutes, take it out and wash it with water until there is no alkali solution residue, then put it into water and heat it for 20 minutes, take it out and put it into an oven at 60°C to dry it to obtain alkali-treated rush. Grind the alkali-treated rush into powder and sieve it with a 500-mesh sieve to obtain a powder particle size of ≤30.8μm. Mix the rush powder with the PVA solution obtained in step S1 and stir it evenly, wherein the mass ratio of rush to PVA is 1:1, then add the crosslinker solution and continue stirring to obtain a mixed solution. The preparation method of the crosslinker solution is as follows: weigh 0.25g of citric acid and 0.125g of sodium hypophosphite and put them into 2mL of water to fully dissolve them.

[0055] S3, evenly coating the mixed solution obtained in step S2 on gauze, and then performing freeze-thaw treatment three times, wherein the freeze-thaw treatment refers to freezing at -20°C for 12 hours, then taking it out and thawing it at room temperature for 3 hours, performing freeze-thaw treatment three times, i.e. repeating the above steps three times, and finally obtaining rush hemostatic gauze.

[0056] Example 2-3 The difference between Example 2-3 and Example 1 is that the particle size of the rush powder in step S2 is ≤22 μm (corresponding to using a 700-mesh sieve, Example 2) and ≤51.3 μm (corresponding to using a 300-mesh sieve, Example 3). Other details are the same as in Example 1 and will not be repeated here.

[0057] See Figure 1 Shown is the physical diagram of rush hemostatic gauze, wherein, a is the rush hemostatic gauze (powder particle size≤22 μm) prepared by embodiment 2, b is the rush hemostatic gauze (powder particle size≤30.8 μm) prepared by embodiment 1, and c is the rush hemostatic gauze (powder particle size≤51.3 μm) prepared by embodiment 3. It can be seen that the gel layer on gauze b surface is evenly distributed, and gauze a surface is slightly uneven due to the agglomeration phenomenon of rush. Gauze c surface is too thick because rush particles, and gel distribution is also slightly uneven, and feel is relatively poor.

[0058] Examples 4-5 and Comparative Example 1 The difference between Examples 4-5 and Comparative Example 1 and Example 1 is that the concentration of PVA in step S1 is 5% (Example 4), 15% (Example 5), and 20% (Comparative Example 1), respectively. Other details are the same as in Example 1 and will not be repeated here.

[0059] See Figure 2The following are scanning electron microscope (SEM) images of the rush hemostatic gauze prepared in Example 1 and Example 4, wherein a is the SEM image of the rush hemostatic gauze prepared in Example 4, and b is the SEM image of the rush hemostatic gauze prepared in Example 1. Figure 2 In a, the gel skeleton formed by rush and PVA wraps the gauze inside, but some gauze fibers are still exposed outside. Figure 2 The gauze in b is evenly wrapped, and the exposed area is significantly reduced, indicating that too low a PVA concentration will lead to insufficient cross-linking between rush and PVA, and the strength of the formed gel skeleton is insufficient, resulting in reduced adhesion of rush.

[0060] The rush hemostatic gauze prepared in Example 5 and Comparative Example 1 was relatively hard, especially Comparative Example 1, which had a poor hand feel.

[0061] A hydrogel material with similar mechanical properties and surface characteristics to human skin was selected as the simulated wound material, and the adhesion of the hemostatic gauze prepared in Example 1 and Example 4 and ordinary gauze was tested. The size of the simulated wound material was 5cm×5cm and the thickness was 2-3mm. The test temperature was 37±1°C, the relative humidity was 50-60%, and the instrument used for the test was an INSTRON3400 series universal testing machine. The test steps were as follows: the simulated wound material was spread on a smooth test platform, fixed with a special clamp, a gauze to be tested with a size of 3cm×3cm was taken and covered on the center of the simulated wound material, a cylindrical weight of 500g was placed on the surface of the gauze and evenly pressed for 1 minute to promote the formation of stable adhesion between the gauze and the simulated wound. Then, the hook connected to the mechanical instrument was gently hooked on a corner of the gauze, and a vertical upward pulling force was slowly applied at a rate of 0.1N / s until the gauze was separated from the simulated wound, and the maximum peeling tension (N) at the moment the gauze was separated from the simulated wound was recorded. According to the formula adhesion (N / cm 3 ) = Maximum peeling force (N) ÷ contact area (cm 2 ) to calculate the adhesion force. Use the same method to measure 5 pieces of gauze of the same specifications and take the average adhesion force. The test results are shown in Table 1.

[0062] Table 1 As shown in Table 1, it can be seen that as the PVA concentration increases, the adhesion between the gauze and the wound surface shows a trend of first increasing and then decreasing. This is because when the PVA concentration is too low, the gel skeleton structure wrapped on the surface of the gauze fiber is loose and the mechanical strength is insufficient. After swelling, it is easy to shrink the contact area due to its own deformation, weaken the interfacial force, and thus lead to a decrease in adhesion; when the PVA concentration is too high, the molecular chains are excessively aggregated to form a dense layer with strong rigidity, resulting in a decrease in the flexibility of the gel layer wrapped on the surface of the gauze fiber and a decrease in the degree of adhesion to the wound; when the PVA concentration is 10%, the molecular chain stacking degree of the gel layer is moderate, with certain mechanical strength and flexibility, and good pore connectivity. After contact with blood, it can quickly absorb body fluids and swell moderately. The swollen material can further fit closely to the wound surface, thereby improving the adhesion. Properly improving the adhesion can make the rush gel wrapped on the surface of the gauze fit closely to the wound, which is conducive to fully exerting its hemostatic effect. When the PVA concentration is 10%, the adhesion of the gauze is moderate, which can ensure a closer fit to the wound without being difficult to peel off during dressing changes, causing secondary damage to the wound. This is the optimal concentration for preparing rush hemostatic gauze.

[0063] Examples 6-7 The difference between Example 6-7 and Example 1 is that the mass ratio of rush to PVA in step S2 is 1:1.5 (Example 6) and 1.5:1 (Example 7), respectively. The rest is the same as Example 1 and will not be repeated here.

[0064] See Figure 3 As shown, during the preparation process of Example 7, precipitation occurred due to the high proportion of rush in the mixed solution, resulting in slightly uneven coating (i.e., the rush was unevenly distributed on the gauze surface).

[0065] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that rush is not added to the hemostatic gauze, that is, step S2 is deleted, and the PVA solution is directly coated on the gauze in step S3. Other steps are the same as those in Example 1 and will not be repeated here.

[0066] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that chitosan hemostatic gauze is prepared using chitosan, and the preparation steps are as follows: Chitosan powder was dissolved in 5% dilute acetic acid, and a 0.2% glutaraldehyde solution was added for cross-linking reaction for 2 hours. Then, medical gauze was immersed in the reaction solution for 10-30 minutes, and most of the solvent was drained off and dried to form a chitosan film on the fiber surface to obtain chitosan hemostatic gauze.

[0067] The hemostatic properties and antibacterial properties of the hemostatic gauze prepared in Example 1, Examples 4-7 and Comparative Examples 1-3 and ordinary gauze were tested: (1) Hemostatic performance test The hemostasis experiment follows animal ethics standards and uses a standardized animal model. This experiment uses a rabbit femoral artery injury model. The final experimental data records the hemostasis time and amount of hemostasis. The coagulation experiment uses a rabbit femoral artery injury model. The main steps are to separate the rabbit's femoral artery and transect 1 / 2 of the blood vessel diameter, then cover the wound with a test hemostatic gauze, use sterile tweezers to simulate clinical pressure and press lightly, and at the same time loosen the artery clamp to allow blood flow to impact the gauze. If the gauze bleeds, do not replace it, just superimpose it and record the number of times. Record the hemostasis time from the time the gauze is covered to when there is no bleeding for 30 consecutive seconds, weigh the blood-stained gauze, and calculate the weight difference of the gauze before and after blood collection to obtain the amount of bleeding. The test results are shown in Table 2.

[0068] (2) Antibacterial performance test The antibacterial rate was calculated according to the formula: antibacterial rate (%) = (number of colonies in the control group - number of colonies in the experimental group) / number of colonies in the control group × 100. According to the standard, an antibacterial material with an antibacterial rate greater than 90% is qualified. The test was conducted using the shaking flask method. The experimental steps were as follows: 0.1 g of shredded hemostatic gauze was mixed with a bacterial suspension (10 mL, 1×10 6 CFU / mL) were placed in shake flasks and shaken at 37°C (150 rpm) for 24 hours. After dilution, the plates were spread and the colonies were counted to evaluate the inhibition rate. The test results are shown in Table 2.

[0069] Table 2 See shown in Table 2, the shorter the hemostatic time and the less the bleeding volume, the better the hemostatic effect of representative gauze. It can be seen that the hemostatic effect of chitosan hemostatic gauze (comparative example 3) and rush hemostatic gauze (embodiment 1-7 and comparative example 1) is significantly better than the hemostatic gauze (comparative example 2) and common gauze that surface is wrapped with gel, and the hemostatic effect of rush hemostatic gauze is significantly better than chitosan hemostatic gauze. Wherein, along with the increase of PVA concentration, hemostatic time and bleeding volume present the trend of first reducing and then increasing, and when concentration is 10%, hemostatic effect is best, this is because, on the one hand, when PVA concentration is 10%, the adhesion of gauze is best, can be closely fitted with wound surface, avoid the gap oozing blood caused by deformation in use, can better adsorb blood simultaneously, promote coagulation factor to gather. On the other hand, when PVA concentration is 10%, the porosity of the gel layer of gauze surface parcel is high, and pore connectivity is better, can rapidly adsorb blood, improve hemostasis efficiency. In addition, when the mass ratio of rush to PVA is less than or equal to 1:1, the hemostatic effect of the gauze increases with the increase in the proportion of rush, and when the mass ratio is greater than 1:1, there is no longer a significant improvement (the effects of Example 1 and Example 7 are similar). From the perspective of saving materials and reducing preparation difficulty (uneven coating is easy when the mass ratio is 1.5:1), the best mass ratio of rush to PVA is 1:1.

[0070] Therefore, the parameters in Example 1 are the optimal combination. The rush hemostatic gauze prepared by this method has the properties of efficient liquid absorption, rapid coagulation and structural stability, and has moderate adsorption force. It ensures that the gauze fits tightly to the wound surface and is not easy to cause secondary damage to the wound.

[0071] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that, in step S3, the mixed solution is first subjected to freeze-thaw treatment 3 times, sliced ​​after obtaining gel, and covered on the gauze surface. Other examples are the same as in Example 1 and will not be repeated here. The surface slices of the rush hemostatic gauze prepared in Comparative Example 3 are difficult to be firmly combined with the gauze and are easily fallen off during use.

[0072] Comparative Example 4 Comparative Example 4 differs from Example 1 in that, in step S3, the mixed solution obtained in step S2 is evenly coated on gauze and then freeze-dried at -80°C for 48 hours. Other steps are the same as in Example 1 and are not further described here. The rush hemostatic gauze prepared in Comparative Example 4 becomes hardened after freeze-drying, affecting the feel of the gauze.

[0073] The blood and cell compatibility of the rush hemostatic gauze prepared in Example 1 was tested according to ISO 10993-4 and ISO 10993-5, wherein the hemolysis rate was required to be ≤10% and the cell survival rate was ≥75%. The cytotoxicity test procedures were as follows: 1. Extract Preparation: Cut the rush hemostatic gauze into 2 cm × 2 cm pieces and soak it in serum-containing culture medium at 37°C for 72 h.

[0074] 2. Cell culture: Inoculate L929 mouse fibroblasts and culture in the extract for 24-48 hours.

[0075] 3. Detection method: MTT assay was used to determine cell viability.

[0076] The test steps for blood compatibility assessment are as follows: The gauze was soaked in 37°C physiological saline for 24 hours to obtain an extract, which was mixed with a fresh rabbit red blood cell suspension and incubated at 37°C for 1 hour. The mixture was then centrifuged and the absorbance of the supernatant at 545 nm was measured. The hemolysis rate was calculated according to the formula: hemolysis rate = (sample absorbance - negative control absorbance) / (positive control absorbance - negative control absorbance) × 100%.

[0077] The cell viability and hemolysis rate data obtained from the test are shown in Table 3.

[0078] Table 3 As shown in Table 2, the cell survival rate of the rush hemostatic gauze prepared in Example 1 was 92%, and the hemolysis rate was 4%, indicating that it had good biocompatibility.

[0079] In summary, the present application provides a method for preparing rush hemostatic gauze, which uses PVA as a matrix, mixes powdered rush with a PVA solution, and then evenly coats the mixture on medical gauze. The rush hemostatic gauze is prepared through a cyclic freeze-thaw treatment. The present application also regulates the preparation conditions such as the concentration of PVA, the mass ratio of rush to PVA, and the particle size of rush powder to adjust the prepared gel structure in order to balance the antibacterial and hemostatic properties and the feel of the hemostatic gauze. When the PVA concentration is 10%, the mass ratio of rush to PVA is 1:1, and the rush particle size is ≤30.8μm (using a 500-mesh sieve), the encapsulated gel structure formed on the surface of the gauze has both density and flexibility, which can support the uniform distribution of rush powder and seal the wound surface through moderate swelling. The adhesion is 0.3N / cm higher than that of ordinary gauze. 3 The hemostatic time and bleeding volume are only half of those of ordinary gauze. The hemostatic time is 58s shorter than that of chitosan hemostatic gauze, and the bleeding volume is 0.36g less.

[0080] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are merely examples, and any embodiments having substantially the same structure and effect as the technical concept within the scope of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the present application, any other embodiments that can be conceived by those skilled in the art and that combine some of the constituent elements in the embodiments are also included in the scope of the present application.

Claims

1. A method for preparing rush hemostatic gauze, characterized in that: The steps include: S1, mixing polyvinyl alcohol and water under stirring conditions, standing at room temperature for a period of time, heating in a water bath and stirring to fully dissolve the polyvinyl alcohol to obtain a polyvinyl alcohol solution with a concentration of 5-15% by weight; S2, grinding the alkali-treated rush into powder, mixing it with the polyvinyl alcohol solution obtained in step S1 and stirring it evenly, then adding the crosslinking agent solution, and continuing to stir evenly to obtain a mixed solution; S3, evenly coating the mixed solution obtained in step S2 on gauze, and then performing freeze-thaw treatment 2-4 times to obtain rush hemostatic gauze.

2. The method for preparing the rush hemostatic gauze according to claim 1, wherein The mass ratio of rush to polyvinyl alcohol is 1:(0.67-1.5).

3. The method for preparing the rush hemostatic gauze according to claim 1, wherein In step S3, the freeze-thaw treatment step includes freezing at -(15-25)°C for 12-16 hours, and then taking it out and thawing it at room temperature for 2-4 hours.

4. The method for preparing the rush hemostatic gauze according to claim 1, wherein In step S1, the temperature of the water bath heating and stirring is 80-90°C, and the time is greater than or equal to 30 minutes; in step S1, standing at room temperature for a period of time specifically refers to standing at room temperature for 20-60 minutes.

5. The method for preparing the rush hemostatic gauze according to claim 1, wherein In step S2, the rush is polished and then sieved through a 300-700 mesh sieve.

6. The method for preparing the rush hemostatic gauze according to claim 1, wherein: In step S2, the cross-linking agent is a mixture of citric acid and sodium hypophosphite.

7. The method for preparing the rush hemostatic gauze according to claim 6, wherein: The mass ratio of the citric acid to the sodium hypophosphite is (3-1):

1.

8. The method for preparing the rush hemostatic gauze according to claim 1, wherein: In step S2, the specific steps of alkali treatment include placing the rush in an alkali solution and heating it for 15-25 minutes, taking it out and washing it with water, then placing it in the alkali solution again and heating it for 15-25 minutes, taking it out and washing it with water until no alkali solution remains, then placing it in water and heating it for 10-25 minutes, and drying it.

9. A rush hemostatic gauze, characterized in that: The rush hemostatic gauze is prepared according to the preparation method of rush hemostatic gauze according to any one of claims 1-8.

10. The rush hemostatic gauze according to claim 9, characterized in that: The gel skeleton formed by cross-linking rush and PVA wraps the gauze fibers inside.

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